Bendamustine/Rituximab Followed by Venetoclax and Rituximab for Treatment of Chronic Lymphocytic Leukemia

NCT03609593 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: AAAR6357
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the efficacy of bendamustine and rituximab (BR) followed by venetoclax for 12 months. The total time on therapy is 15 months. Bendamustine and rituximab is a commonly used treatment for CLL. Venetoclax is an oral drug that blocks a protein called BCL-2 which is present on CLL cells. It is approved for patients with relapsed (the cancer has come back) or refractory (the cancer did not respond) CLL who harbor a deletion in the short arm of chromosome 17 \[del(17p)\]. When this drug is used by itself, many patients needed to be admitted to the hospital to monitor for a complication known as tumor lysis syndrome. This is an oncologic emergency that is caused by massive destruction of tumor cells with the release of large amounts of electrolytes and other molecules into the blood that can lead to renal failure and potentially death.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Chronic Lymphocytic Leukemia (CLL); Leukemia; Bendamustine; Rituximab; Venetoclax

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR) after the completion of all therapy

  Proportion of patients with reduction in tumor burden of a predefined amount

  15 months

Study Arms (1)

BR followed by venetoclax and rituximab

EXPERIMENTAL

Subjects will be on Bendamustine 50-90 mg/m2 on days 1-2 for three cycles with each cycle being 28 days, and Rituximab 375 mg/m2 on day 1 or days 1-2 for three cycles with each cycle being 28 days. Venetoclax will then be started in a step-wise fashion per the package insert.

Drug: Bendamustine; Drug: Venetoclax; Drug: Rituximab

Interventions

Venetoclax DRUG

Venetoclax: 12 cycles Venetoclax will then be started after 3 cycles of BR. Dosing for venetoclax will be in a step wise fashion as follows: * Cycle 4 days 1-7 (Week 1): 20 mg once daily * Cycle 4 days 8-14 (Week 2): 50 mg once daily * Cycle 4 days 15-21 (Week 3): 100 mg once daily * Cycle 4 days 22-28 (Week 4): 200 mg once daily * Cycle 4 day 29 and thereafter (Week 5 and on): 400 mg once daily; continue until disease progression, unacceptable toxicity, or 12 cycles duration.

Also known as: ABT-199, Venclexta

BR followed by venetoclax and rituximab

Rituximab DRUG

For cycles 1 through 3, subjects will receive BR on days 1 and 2. For cycles 5-10, subjects will receive rituximab monotherapy at 375 mg/m2 (cycle 5) or rituximab at 500 mg/m2 (cycles 6-10) on day 1 (or days 1 and 2 if split-dose).

Also known as: Rituxan

BR followed by venetoclax and rituximab

Bendamustine DRUG

Subjects will receive Bendamustine 50-90 mg/m2 on days 1-2 for three cycles with each cycle being 28 days.

Also known as: Treanda

BR followed by venetoclax and rituximab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years of age.
• Diagnosed with CLL
• To be considered CLL, the subject must have an absolute lymphocytosis in the blood of at least 5,000 lymphocytes per microliter, or bone marrow lymphocytosis greater than or equal to 30% of all nucleated cells.
• Histologic and immunophenotypic analysis should demonstrate small to moderate size lymphocytes with flow cytometry demonstrating a certain population of lymphocytes.
• No prior therapy for their disease. Topical or inhaled corticosteroids are permitted for other medical conditions, ie asthma or dermatologic reasons.
• Eastern Oncology Cooperative Group (ECOG) performance score of ≤ 2.
• Subjects with autoimmune hemolytic anemia or autoimmune thrombocytopenia will be eligible for treatment on this protocol regardless of disease stage upon discussion with the principal investigator.
• An absolute neutrophil count \> 1.0 109/L; hemoglobin \> 8 g/dL; or a platelet count \> 50 x 109/L (unless due to bone marrow failure).
• Adequate hepatic function
• activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5x the upper limit of reference ranges.
• Ability to understand and the willingness to sign a written informed consent document.
• Women of child-bearing potential and men must agree to use adequate contraception (see below) for at least 90 days prior to study entry and for the duration of study participation.
• For women of childbearing potential (WCBP): a negative serum β-human chorionic gonadotropin (βhCG) pregnancy test must be performed within 1 week before randomization (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 24 consecutive months \[women ≤ 55 years\] or 12 consecutive months \[women \> 55 years\]).
• Male and female subjects who are not surgically sterile or postmenopausal must be willing to use medically acceptable methods of birth control from the first dose of study drug to 30 days after the last dose of study drug. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception.

You may not qualify if:

• Subjects who have been previously treated for CLL or small lymphocytic lymphoma (SLL), except with corticosteroids for symptom relief.
• Treatment with any of the following within 7 days prior to the first dose of study drug:
• Steroid therapy for anti-neoplastic intent
• moderate or strong cytochrome P450 3A (CYP3A) inhibitors
• moderate or strong CYP3A inducers
• Subject has known allergy to both xanthine oxidase inhibitors and/or rasburicase.
• Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the investigator would adversely affect his/her participating in this study.
• Subject has evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
• Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
• Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate.
• Subject is known to be positive for HIV. (HIV testing is not required.)
• New York Heart Association (NYHA) class II-IV heart failure or arrhythmia requiring treatment.
• Pregnant or lactating women. Women and men of childbearing age should use effective contraception.
• Subject has a history of active malignancies other than CLL within the past 2 years prior to study entry with the exception of: adequately treated in situ carcinoma of the cervix uteri, adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin, or previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
• Subjects may receive intravenous immunoglobulin (IVIG) for hypogammaglobulinemia while on protocol. Subjects may receive erythropoietin, filgrastim, pegfilgrastim, or sargramostim while on protocol.

Sponsors & Collaborators

• Nicole Lamanna: lead

Study Sites (1)

Columbia University Irving Medical Center / NewYork-Presbyterian Hospital

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia

Interventions

Bendamustine Hydrochloride; venetoclax; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nicole Lamanna, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Clinical Professor of Medicine

Study Record Dates

• First Submitted: July 25, 2018
• First Posted: August 1, 2018
• Study Start: November 12, 2018
• Primary Completion: January 27, 2026
• Study Completion: January 27, 2026
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)